Detecting adaptive immunity to coronavirus

Abstract

Provided are devices, systems, methods and kits for determining whether a subject is immune to an infection by a disease-causing pathogen by measuring neutralizing antibodies against the disease-causing pathogen in a biological sample from the subject. The devices, systems, methods, and kits described herein are useful for confirming whether a vaccine against the disease-causing pathogen has elicited enough neutralizing antibodies to prevent a later infection, or lessen severity of disease caused by, the disease-causing pathogen. Such devices, systems, methods, and kits are also useful for detecting an infection in the subject.

What is claimed: 
     
         1 . A method for processing a biological sample, the method comprising:
 (a) bringing a capillary blood sample into contact with (i) a first polypeptide comprising an Angiotensin-converting enzyme 2 (ACE2) polypeptide or a portion thereof capable of binding to a spike protein of a coronavirus and (ii) a second polypeptide comprising the spike protein of the coronavirus or an ACE2-binding portion of the spike protein under conditions sufficient cause the first polypeptide and the second polypeptide to form a detectable binding complex; and   (b) detecting the detectable binding complex, which detecting is indicative of an absence or a low level of neutralizing antibodies against the spike protein relative to a known level of the neutralizing antibodies, wherein the neutralizing antibodies block binding between the spike protein or the ACE2-binding portion thereof and the ACE2 polypeptide or the portion thereof under conditions otherwise suitable for binding.   
     
     
         2 . The method of  claim 1 , wherein the capillary blood sample has a volume comprising less than 1 milliliter (mL). 
     
     
         3 . The method of  claim 2 , wherein the volume comprises less than 100 microliters (μl). 
     
     
         4 . The method of  claim 1 , wherein the coronavirus is a severe acute respiratory syndrome (SARS) coronavirus. 
     
     
         5 . The method of  claim 4 , wherein the SARS coronavirus is SARS coronavirus 2 (SARS-CoV-2). 
     
     
         6 . The method of  claim 1 , wherein the capillary blood sample is obtained from a human subject. 
     
     
         7 . The method of  claim 1 , wherein the method does not comprise a wash step whereby the first polypeptide and the second polypeptide that is unbound following (a) is substantially removed prior to detecting in (b). 
     
     
         8 . The method of  claim 1 , wherein detecting the binding complex in (b) comprises measuring a fluorescence signal. 
     
     
         9 . The method of  claim 8 , wherein the fluorescence signal is inversely correlated with a level of neutralizing antibodies in the capillary blood sample. 
     
     
         10 . The method of  claim 1 , wherein the binding complex is immobilized to a solid support. 
     
     
         11 . A method for processing a biological sample, the method comprising:
 (a) receiving a biological sample from a subject, wherein the biological sample was obtained from the subject by one or more finger pricks;   (b) bringing the biological sample into contact with (i) a first polypeptide comprising an Angiotensin-converting enzyme 2 (ACE2) polypeptide or a portion thereof capable of binding to a spike protein of a coronavirus and (ii) a second polypeptide comprising the spike protein of the coronavirus or an ACE2-binding portion of the spike protein under conditions sufficient cause the first polypeptide and the second polypeptide to form a detectable binding complex; and   (c) detecting the detectable binding complex, which detecting is indicative of an absence or a low level of neutralizing antibodies against the spike protein relative to a known level of the neutralizing antibodies, wherein the neutralizing antibodies block binding between the spike protein or the ACE2-binding portion thereof and the ACE2 polypeptide or the portion thereof under conditions otherwise suitable for binding.   
     
     
         12 . The method of  claim 11 , wherein the biological sample has a volume comprising less than 1 milliliter (mL). 
     
     
         13 . The method of  claim 12 , wherein the volume comprises less than 100 microliters (μl). 
     
     
         14 . The method of  claim 11 , wherein the coronavirus is a severe acute respiratory syndrome (SARS) coronavirus. 
     
     
         15 . The method of  claim 14 , wherein the SARS coronavirus is SARS coronavirus 2 (SARS-CoV-2). 
     
     
         16 . The method of  claim 11 , wherein the subject is a human subject. 
     
     
         17 . The method of  claim 11 , wherein the method does not comprise a wash step whereby the first polypeptide and the second polypeptide that is unbound following (a) is substantially removed prior to detecting in (c). 
     
     
         18 . The method of  claim 11 , wherein detecting the binding complex in (b) comprises measuring a fluorescence signal. 
     
     
         19 . The method of  claim 18 , wherein the fluorescence signal is inversely correlated with a level of neutralizing antibodies in the biological sample. 
     
     
         20 . The method of  claim 11 , wherein the binding complex is immobilized to a solid support. 
     
     
         21 . A method for processing a biological sample, the method comprising:
 (a) obtaining less than 1 milliliter (mL) of a biological sample from a subject;   (b) bringing the biological sample into contact with (i) a first polypeptide comprising an Angiotensin-converting enzyme 2 (ACE2) polypeptide or a portion thereof capable of binding to a spike protein of a coronavirus and (ii) a second polypeptide comprising the spike protein of the coronavirus or an ACE2-binding portion of the spike protein under conditions sufficient cause the first polypeptide and the second polypeptide to form a detectable binding complex; and   (c) detecting the detectable binding complex, which detecting is indicative of an absence or a low level of neutralizing antibodies against the spike protein relative to a known level of the neutralizing antibodies, wherein the neutralizing antibodies block binding between the spike protein or the ACE2-binding portion thereof and the ACE2 polypeptide or the portion thereof under conditions otherwise suitable for binding.   
     
     
         22 . The method of  claim 21 , wherein the biological sample comprises a volume comprising less than 500 μl when it is obtained in (a). 
     
     
         23 . The method of  claim 22 , wherein the volume comprises less than 100 μl. 
     
     
         24 . The method of  claim 21 , wherein the coronavirus is a severe acute respiratory syndrome (SARS) coronavirus. 
     
     
         25 . The method of  claim 24 , wherein the SARS coronavirus is SARS coronavirus 2 (SARS-CoV-2). 
     
     
         26 . The method of  claim 21 , wherein the subject is a human subject. 
     
     
         27 . The method of  claim 21 , wherein the method does not comprise a wash step whereby the first polypeptide and the second polypeptide that is unbound following (a) is substantially removed prior to detecting in (c). 
     
     
         28 . The method of  claim 21 , wherein detecting the binding complex in (c) comprises measuring a fluorescence signal. 
     
     
         29 . The method of  claim 28 , wherein the fluorescence signal is inversely correlated with a level of neutralizing antibodies in the biological sample. 
     
     
         30 . The method of  claim 21 , wherein the binding complex is immobilized to a solid support.